β-Amino acids are widely used intermediates for the synthesis of biologically active compounds such as β-lactams and β-peptides. N-substitution of β-peptides exhibits increased potency and selectivity because of enhanced hydrophobicity, improved bioavailability and metabolic stability. Ring op of aziridines, which is an important and widely used protocol due to ease of preparation, ring strain and high reactivity, is increasingly appreciated because of their application as versatile building blocks for the synthesis of many nitrogen containing biologically interesting molecules.
Although β-amino nitrites are conveniently prepared by the ring opening of aziridines with trimethylsilyl cyanide, bromoacetonitrile, alkali cyanide, the unsatisfactory selectivity, low yield and use of hygroscopic/hazardous chemicals make these methodologies less attractive. Moreover, post alkylation of β-amino nitriles/acids and related peptide is very difficult endeavor.
Synthesis of β-amino nitriles by the nucleophilic ring opening of N-nosyl aziridines with cyanide ions followed by hydrolysis of corresponding nitrites to give N-nosyl β-amino acids is disclosed in Tetrahedron 2001, 57, 7665. The inherent disadvantages are the use of toxic reagents and cumbersome methodology. Synthesis of β-amino nitrites from aldimines and bromoacetonitrile in presence of tin powder and trimethylsilyl chloride is disclosed in Synth. Comm. 1997, 27, 3175. The inherent disadvantage is the usage of expensive reagents.
The ring opening reaction of aziridine with trimethylsilyl compound triggered by tetrabutylammonium fluoride to give corresponding products regioselectively is disclosed in J. Org. Chem. 2000, 65, 1344. This disclosure provides the protocol for the ring opening reaction of aziridine to afford cyano, azido, or chloroamines. However, the inherent disadvantages of this procedure are the use of hygroscopic silyl compound, unsatisfactory selectivity and moderate yield in some cases.
The reaction of Schiff bases such as N-benzylideneanilines with superoxide ion in acetonitrile under mild conditions to yield cyanomethyl adducts is disclosed in Bull. Chem. Soc. Jpn, 1986, 59, 3323. The inherent disadvantages are number of byproducts obtained along with the required amino nitrile, lengthy procedure, non-selectivity and non-catalytic nature of the reaction. Tetrahedron Lett. 1990, 31, 6379, discloses the Yb(CN)3 catalyzed ring opening of aziridine with trimethylsilyl cyanide resulting in the formation of β-amino nitrile. The inherent disadvantage is the critical preparation of catalyst, handling, storage and non-reusability. Preparation of chiral β-N,N-dibenzylamino nitrites in enantiomerically pure form from α-amino acids by deprotonation and stereoselective alkylation is described in Tetrahedron Lett. 1994, 47, 8769. The drawbacks are longer reaction times and usage of multistep procedure. The reaction of N-diphenyl phosphinyl protected aziridines with a range of nucleophiles including trimethylsilylnitrile is reported in Synlett 1994, 145. The drawback is the use of expensive reagents and moderate yields.